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Table 2 Pre- and peri-natal factors associated with the onset of Tourette’s syndrome (TS), and the presence of comorbidity

From: Prenatal risk factors for Tourette Syndrome: a systematic review

Factors

Results (Cases vs. Controls)*

P value

Case number

Control number

Note

Reference

Demographic factors

      

Mother's age

25.69 (5.29) vs. 25.12 (5.2)

p = 0.33

92

460

Matched analysis

Burd 1999 [11]

 

20 (1.4) vs. 23 (3.4)

p < 0.01

25

25

 

Khalifa 2005 [13]

 

29.8 (4.5) vs. 29.6

 

66

1174999

Adjusted for birth year

Shimada 2012 [20]

 

TS: 28.9 (4.4), TS + ADHD: 28.1 (5.3), Control: 28.3 (4.1)

NS

TS: 45, TS + ADHD:60

65

 

Motlagh 2010 [17]

Father's age

28.87 (6.25) vs. 27.78 (5.96)

p = 0.11

92

460

Matched analysis

Burd 1999 [11]

 

31.9 (5.0) vs. 32.7

NS

65

1174999

Adjusted for birth year

Shimada 2012 [20]

 

TS: 30.9 (5.0), TS + ADHD: 30.2 (6.2), Control: 30.4 (5.0)

NS

TS: 45, TS + ADHD:60

65

 

Motlagh 2010 [17]

Mother's education

12.90 (2.11) vs. 12.64 (1.92)

p = 0.24

92

460

Matched analysis

Burd 1999 [11]

Father's education

12.69 (2.44) vs. 12.67 (2.15)

p = 0.96

92

460

Matched analysis

Burd 1999 [11]

Parent's education

TS: 15.5 (2.0), TS + ADHD: 14.9 (1.8), Control: 15.3 (2.0)

NS

TS: 45, TS + ADHD:60

65

 

Motlagh 2010 [17]

Mean socioeconomic status

TS: 50.4 (2.7), TS + ADHD: 47.4 (10.6), Control: 48.5 (10.7)

NS

TS: 45, TS + ADHD:60

65

 

Motlagh 2010 [17]

Socio-economic status, parental education or divorce rate

No difference (no data provided)

NS

25

25

 

Khalifa 2005 [13]

Marital status

4/92 vs. 36/460

p = 0.93

92

460

 

Klug 2003 [14]

Pre-conception condition

      

Major diseases before pregnancy or pre-existing medical conditions

(20/42 vs. 21/43) OR = 0.95, 95% CI = 0.41-2.23

p = 0.91

42

43

 

Kondo 1982 [15]

 

TS vs. Control (1/45 vs. 4/65); TS + ADHD vs. Control (4/60 vs. 4/65)

NS

TS: 45, TS + ADHD:60

65

 

Motlagh 2010 [17]

Pre-natal period

      

Month prenatal care began

2.47 (1.27) vs. 3.01 (1.40)

p = 0.001

92

460

Matched analysis

Burd 1999 [11]

Prenatal visits

10.00 (3.57) vs. 8.51 (3.22)

p < 0.001

92

460

Matched analysis

Burd 1999 [11]

Prenatal care begun after first trimester

OR = 0.49 (0.27-0.90), (14/92 vs. 123/460)

p = 0.03

92

460

 

Burd 1999 [11]

Minor physical anomalies (numbers)

5.46 (2.15) vs. 1.11(1.18); Mann–Whitney U-test 49.50, -Z = -4.92

p = 0.001

24

24

 

Csabi 2008 [12]

Number of prenatal problems

Presence of ADHD, OR = 2.97, 95% CI: 1.27-6.94

p = 0.02

180

  

Mathews 2006 [26]

Disordered pregnancies

(12/42 vs. 15/43) OR = 0.75, 95% CI = 0.30-1.87

p = 0.53

42

43

 

Kondo 1982 [15]

Any pregnancy complication

Male TS vs. Female TS: 63% vs. 83%

NS

46 M

7 F

 

Santangelo 1994 [19]

 

TS + OCD vs. TS: 67% vs. 65%

NS

15

34

 

Santangelo 1994 [19]

One or more pregnancy complication

17/51 vs. 9/51 (OR = 2.33, 95% CI = 0.92-5.89)

p = 0.07

51

51

 

Pasamanick 1956 [18]

 

TS + ADHD: 27/60, Control: 16/65

p = 0.01

TS + ADHD:60

65

 

Motlagh 2010 [17]

 

TS: 17/45, Control: 16/65

NS

TS: 45

65

 

Motlagh 2010 [17]

Maternal hypertension

TS + ADHD vs. TS, OR = 1.04 (95% CI: 0.44-2.42)

p = 0.93

181

172

Unadjusted OR

Pringsheim 2009 [21]

Severe psychosocial stress

TS vs. Control (10/45 vs. 5/62, OR = 2.6, 95% CI = 0.08-8.7, p = 0.11); TS + ADHD vs. Control (11/55 vs. 5/62, OR = 3.1, 95% CI = 0.9-11.1, p = 0.07)

p = 0.11 and 0.07

TS: 45, TS + ADHD:60

65

Adjusted for gender

Motlagh 2010 [17]

Antibiotics exposure in pregnancy

TS: 11/45, TS + ADHD: 11/60, Control: 6/65

both p < 0.05

TS: 45, TS + ADHD:60

65

 

Motlagh 2010 [17]

Medication/procedures

Male TS vs. Female TS: 37% vs. 50%

NS

46 M

7 F

 

Santangelo 1994 [19]

 

TS + OCD vs. TS: 27% vs. 44%

NS

15

34

 

Santangelo 1994 [19]

Number of medications exposed to in utero

Presence of ADHD, OR = 0.50, 95% CI: 0.25-1.00

p < 0.05

180

  

Mathews 2006 [26]

Maternal smoking (>10 cigarettes/d)

TS vs. Control (3/45 vs. 1/62, OR = 4.6, 95% CI = 0.45-46.6, p = 0.19); TS + ADHD vs. Control (7/60 vs. 1/62, OR = 8.5, 95% CI = 0.97-75.2, p = 0.052)

p = 0.19 and 0.05

TS: 45, TS + ADHD:60

65

Adjusted for gender

Motlagh 2010 [17]

Maternal smoking

TS + ADHD vs. TS, OR = 2.43 (95% CI: 1.23-4.82)

p = 0.01

181

172

Adjusted OR

Pringsheim 2009 [21]

Maternal smoking

Presence of OCD (OR = 8.27, 95% CI = 0.87-78.20)

p = 0.07

180

  

Mathews 2006 [26]

Maternal alcohol exposure

TS + ADHD vs. TS, OR = 0.81 (95% CI: 0.46-1.41)

p = 0.45

181

172

Adjusted OR

Pringsheim 2009 [21]

Coffee, cigarettes, alcohol

Male TS vs. Female TS: 47% vs. 50%

NS

46 M

7 F

 

Santangelo 1994 [19]

 

TS + OCD vs. TS: OR = 5.0, 95% CI: 1.3-19.4

p < 0.05

15

34

 

Santangelo 1994 [19]

Perinatal period

      

Disordered deliveries

(16/42 vs. 14/43) (OR = 1.27, 95% CI = 0.52-3.11)

p = 0.59

42

43

 

Kondo 1982 [15]

Any delivery complication

Male TS vs. Female TS: OR = 9.4, 95% CI: 1.01-87.3

p < 0.05

46 M

7 F

 

Santangelo 1994 [19]

 

TS + OCD vs. TS: 75% vs. 54%

NS

15

34

 

Santangelo 1994 [19]

Operative delivery

TS + ADHD vs. TS, OR = 1.10 (95% CI: 0.71-1.71)

p = 0.66

181

172

Unadjusted OR

Pringsheim 2009 [21]

Forceps delivery

Male TS vs. Female TS: 44% vs. 14%

NS

46 M

7 F

 

Santangelo 1994 [19]

 

TS + OCD vs. TS: OR = 7.9, 95% CI: 3.2-19.5

p < 0.01

15

34

 

Santangelo 1994 [19]

Perinatal disorders: low BW, Asphyxia, severe vomiting, cyanosis, respiratory distress, jaundice, convulsion, high fever, incubator using, exchange transfusion

8/43 vs. 9/43, X^2 = 0.07 (OR = 0.86, 95% CI = 0.30-2.50)

NS (p = 0.79)

43

43

 

Kondo 1982 [15]

Perinatal complications (postnatal jaundice, cord around neck, breech birth, premature birth)

TS + OCS vs. TS only: 5/13 vs. 0/10)

p < 0.01

13

10

Fisher's exact test

Iida 1996 [22]

> 1 hypoxic event

TS vs. Control (17/45 vs. 18/65, OR = 1.4, 95% CI = 0.64-3.3, NS); TS + ADHD vs. Control (18/60 vs. 18/65, OR = 0.9, 95% CI = 0.4-2.2, NS)

NS

TS: 45, TS + ADHD:60

65

Adjusted for gender

Motlagh 2010 [17]

Apgar 1

7.170+/-1.909 vs. 7.517+/-1.623

p = 0.17

53

265

Matched analysis

Burd 1999 [11]

Apgar 5

8.396+/-1.446 vs.8.789+/-1.123

p = 0.03

53

265

Matched analysis

Burd 1999 [11]

Breathing problems at birth

TS + ADHD vs. TS, OR = 1.95 (95% CI: 0.87-4.37)

p = 0.10

181

172

Adjusted OR

Pringsheim 2009 [21]

Combined pre- and peri-natal periods

      

Total with abnormalities of prenatal and perinatal periods

19/51 vs. 13/51 (OR = 1.74, 95% CI = 0.74-4.05)

p = 0.20

51

51

 

Pasamanick 1956 [18]

Reduced optimality in pre-, peri-, and neonatal periods

No statistical differences between cases and controls (no data provided) in reduced optimality

 

25

25

 

Khalifa 2005 [13]

Pre- and perinatal events

TS (26/48 (54%)), Chronic tics (24/48 (50%)) vs. Control (2/30 (6%)); TS: OR = 16.55 (95% CI = 3.54-77.40); Chronic tics: OR = 14.00 (95% CI = 3.00-65.44)

p < 0.001 (both)

TS: 48, chronic tics: 48

30

 

Saccomani 2005 [23]

Neonatal factors

      

Gestation age

39.64 (2.73) vs. 40.04 (3.54)

0.44

92

460

Matched analysis

Burd 1999 [11]

Gestational age (<37 week)

5/106 vs. 62289/1153363

 

106

1153363

 

Shimada 2012 [20]

 

TS + ADHD vs. TS, OR = 3.83 (95% CI: 15.1-9.69)

p < 0.01

181

172

Unadjusted OR

Pringsheim 2009 [21]

Gestational age (<38 week)

TS: 1/45, TS + ADHD: 6/60, Control: 7/65

NS

TS: 45, TS + ADHD:60

65

 

Motlagh 2010 [17]

Gestational age (>42 week)

TS: 4/45, TS + ADHD: 4/60, Control: 2/65

NS

TS: 45, TS + ADHD:60

65

 

Motlagh 2010 [17]

Birth Weight

3342.2+/- 661.38 vs. 3447.7+/-607.71

p = 0.14

92

460

Matched analysis

Burd 1999 [11]

 

TS: 3538+/-530, TS + ADHD: 3438+/-538, Control: 3519+/-755

NS

TS: 45, TS + ADHD:60

65

 

Motlagh 2010 [17]

 

TS vs. Disconcordant Twin: 2228 + -244 vs. 2545 + -216

p = 0.006

6

6

Twins study (paired t test)

Leckman 1987 [16]

Low birth weight (<2500 g)

TS vs. Control (1/45 vs. 2/65, OR = 1.3, 95% CI = 0.11-15.4, NS); TS + ADHD vs. Control (3/57 vs. 2/65, OR = 0.55, 95% CI = 0.08-3.7, NS)

NS

TS: 45, TS + ADHD:60

65

adjusted for gender

Motlagh 2010 [17]

 

TS vs. Control (1/116 vs. 9162/100097, OR = 0.094)

 

116

100097

 

Shimada 2012 [20]

 

TS + ADHD vs. TS, OR = 2.74 (95% CI: 1.03-7.29)

p = 0.04

181

172

Adjusted OR

Pringsheim 2009 [21]

Small for gestational age (<10 percentile)

TS + ADHD vs. TS, OR = 1.13 (95% CI: 0.63-2.04)

p = 0.69

181

172

Unadjusted OR

Pringsheim 2009 [21]

Birth weight above 2500 g

Presence of ADHD, OR = 0.69, 95% CI: 0.52-0.92

p = 0.02

180

  

Mathews 2006 [26]

Birth order

X^2 = 2.53

NS

43

43

 

Kondo 1982 [15]

 

First (78/116 vs. 53947/100118), second (34/116 vs. 34594/100118), > = third (8/116 vs. 11577/100118)

 

116

100118

 

Shimada 2012 [20]

  1. *TS versus controls if not indicated. ADHD: Attention deficit hyperactive disorder; BW: birth weight; CI: confidence interval; NS: non-significant; OCD: Obsessive compulsive disorder; OCS: Obsessive compulsive symptoms; OR: odds ratio; TS: Tourette’s syndrome, statistically significant results shown in bold.